Thermal therapies have important applications in cancer treatment;viz., curative or palliative tumor ablation. High intensity focused ultrasound (HIFU) is an attractive modality for such applications because of its potential to be applied non-invasively (i.e., transcutaneously). Several factors limit the effectiveness of HIFU therapy;viz., the abilities to:(1) develop effective treatment protocols based on a firm understanding of the physics and biology, (2) monitor treatment progression in real time to provide guidance and control, (3) deliver the appropriate thermal dose accurately and efficiently, and (4) register the target and compensate for tissue motion. The project's long term objective is to develop an integrated thermal therapy research system that uses transcutaneous HIFU as the heat source and which would serve as a prototype for future therapy platforms. Specific aims address the needs identified above, development of a research therapy system, and preliminary testing of the system in vivo. Aim 1 is to develop quantitative approaches to HIFU exposimetry and thermal dosimetry, and to validate and refine them for treatment planning. Aim 2 is to refine our algorithms for processing radio frequency ultrasound (US) backscatter data to enable real time monitoring and control of treatment progression produced using HIFU or other thermal therapies. Aim 3 is to develop new HIFU protocols using continuously moving focal zones to produce desired volumetric tissue temperature profiles and lesion geometries, and thus enable accurate and efficient treatment. Although cavitation is often associated with HIFU and can ablate tissues mechanically, we will attempt to devise protocols that minimize its role. Aim 4 is to refine algorithms for pre-treatment multimode image registration (e.g., MR and 3-D US) and for motion compensation using time-of-treatment 2-D US images, and to integrate these algorithms with the HIFU therapy plan, US temperature sensing, and a simple robotic system to build a research US-guided therapy system. Aim 5 is to test the system in acute studies of lesion placement in vivo, and to iteratively refine the system components. A multidisciplinary team approach is taken, involving acoustics, biology, medicine, applied mathematics, engineering, and software development, and will build on a large collective experience with HIFU technology. In vitro and in vivo experimentation, numerical modeling, image processing methods and other engineering aspects will contribute to the overall goal, with close communication between elements to enable rapid feedback and refinements.